Human diploid fibroblast-like cells have a life history which includes a period of rapid, vigorous proliferation, followed by a period of declining proliferative vigor and ultimately the cessation of DNA synthesis and proliferation. SV40 transformed cell lines, derived from diploid fibroblast-like cells have escaped the finite lifespan limitation. The declining proliferative vigor has been interpreted as cell senescence. The subject of this proposal is elucidation of the mechanisms which underlie the regulation of proliferation in human cells. Cultures of young, senescent and transformed human cells, from the same original cell line, provide the full spectrum of proliferative control.